• Component Description
• Eligible Sample
• Description of Laboratory Methodology
• Laboratory Quality Assurance and Monitoring
• Data Processing and Editing
• Analytic Notes
• References
• Codebook
  • SEQN - Respondent sequence number
  • WTSSAPP - Surplus specimen A weights pre-pandemic
  • SSPPMA - PPMA (ng/mL)
  • SSPPMALC - PPMA Cmt code
  • SSMMAC - N-Acetyl-S-methyl-L-cysteine (ng/mL)
  • SSMMACLC - N-Acetyl-S-methyl-L-cysteine Cmt code

National Health and Nutrition Examination Survey

2017-March 2020 Data Documentation, Codebook, and Frequencies

Volatile Organic Compound (VOC) Metabolites: Benzene and Methylating Agent Biomarkers - Urine (Surplus) (P_SSUVCM)

Data File: P_SSUVCM.xpt

First Published: January 2026

Last Revised: NA

Component Description

The NHANES program suspended field operations in March 2020 due to the coronavirus disease 2019 (COVID-19) pandemic. As a result, data collection for the NHANES 2019-2020 cycle was not completed and the collected data are not nationally representative. Therefore, data collected from 2019 to March 2020 were combined with data from the NHANES 2017-2018 cycle to form a nationally representative sample of NHANES 2017-March 2020 pre-pandemic data. These data are available to the public. Please refer to the Analytic Notes section for more details on the use of the data.

Exposure to volatile organic compounds (VOCs) is ubiquitous. Chronic exposure to extremely high levels of some VOCs can lead to cancer and neurocognitive dysfunction. Urinary metabolites of VOCs can be detectable in urine for a longer period of time than the parent VOCs can be detected in blood.

Nearly 200 air toxicants have been associated with adverse health effects in occupational studies or laboratory studies but have not been monitored in general population groups. Measurement of metabolite levels in urine is important to understanding exposure to these compounds in the general population.

PPMA (N-Acetyl-S-(6-hydroxy-2,4-cyclohexadien-1-yl)-L-cysteine) is a metabolite of benzene. Benzene is a group 1 carcinogen according to the IARC and is commonly found in crude oil, gasoline, and tobacco smoke.

MMA (N-Acetyl-S-methyl-L-cysteine) is a biomarker of methylating agents. Methylating agents are associated with tumor formation in the lungs, nasal cavity, liver, trachea, and esophagus in animal models (Konstantinou et. al., 2018).

Eligible Sample

All examined participants age 3 to 5 years and a one-third subsample of examined participants age 6 years and older were eligible.

Description of Laboratory Methodology

This method is a quantitative procedure for the measurement of VOC metabolites in human urine using ultra performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-ESI/MSMS) as described by Alwis et. al. (2012). Chromatographic separation is achieved using an Acquity UPLC® HSS T3 (Part no. 186003540, 1.8 µm x 2.1 mm x 150 mm, Waters Inc.) column with 15 mM ammonium acetate and acetonitrile as the mobile phases. The eluent from the column is ionized using an electrospray interface to generate and transmit negative ions into the mass spectrometer. Comparison of relative response factors (ratio of native analyte to stable isotope labeled internal standard) with known standard concentrations yields individual analyte concentrations.

Laboratory Quality Assurance and Monitoring

Urine specimens are processed, stored, and shipped to the Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta,  GA for analysis.

Detailed instructions on specimen collection and processing are discussed in the NHANES Laboratory Procedures Manual (LPM). Vials are stored under appropriate frozen (–30°C) conditions until they are shipped to National Center for Environmental Health for testing.

The NHANES quality assurance and quality control (QA/QC) protocols meet the 1988 Clinical Laboratory Improvement Amendments mandates. Detailed QA/QC instructions are discussed in the NHANES LPM.

All QC procedures recommended by the manufacturers were followed. Reported results for all assays meet the Division of Laboratory Sciences’ QA/QC performance criteria for accuracy and precision, similar to the Westgard rules (Caudill et. al., 2008).

Data Processing and Editing

Data were received after all analyses were complete. The data were not edited.

Analytic Notes

The COVID-19 pandemic required suspension of NHANES 2019-2020 field operations in March 2020 after data were collected in 18 of the 30 survey locations in the 2019-2020 sample. Data collection was cancelled for the remaining 12 locations. Because the collected data from 18 locations were not nationally representative, these data were combined with data from the previous cycle (2017-2018) to create a 2017-March 2020 pre-pandemic data file. A special weighting process was applied to the 2017-March 2020 pre-pandemic data file. The resulting sample weights in the present file should be used to calculate estimates from the combined cycles. These sample weights are not appropriate for independent analyses of the 2019-2020 data and will not yield nationally representative results for either the 2017-2018 data alone or the 2019-March 2020 data alone. Please refer to the NHANES website for additional information for the NHANES 2017-March 2020 pre-pandemic data, and for the previous 2017-2018 public use data file with specific weights for that 2-year cycle.

Refer to the 2017-2018 and 2019-2020 Laboratory Data Overview for general information on NHANES laboratory data.

There are over 800 laboratory tests performed on NHANES participants. However, not all participants provided biospecimens or enough volume for all the tests to be performed. Additionally, availability of specimens for surplus projects is lower than for other laboratory tests performed on NHANES participants. The specimen availability can also vary by age or other population characteristics. Analysts should evaluate the extent of missing data in the dataset related to the outcome of interest as well as any predictor variables used in the analyses to determine whether additional re-weighting for item non-response is necessary.

Please refer to the NHANES Analytic Guidelines and the on-line NHANES Tutorial for further details on the use of sample weights and other analytic issues.

Subsample Weights

The analytes included in this dataset were measured in all examined participants aged 3-5 years, and in a one-third subsample of participants 6 years and older. Special sample weights are required to analyze these data properly. Specific sample weights for this subsample, WTSSAPP, are included in this data file and should be used when analyzing these data. The sample weights created for this file used the examination sample weight, i.e., WTMECPRP, as the base weight. The base weight was adjusted for additional nonresponse to these lab tests and re-poststratified to the population total using sex, age, and race/Hispanic origin. Participants who were part of the eligible population but who did not provide a urine specimen, or did not have sufficient volume of biospecimens, or who did not give consent for their specimens to be used for future research are included in the file, but they have a sample weight assigned “0” in their records.

Demographic and Other Related Variables

The analysis of NHANES laboratory data must be conducted using the appropriate survey design and demographic variables. The NHANES 2017-March 2020 Demographics File contains demographic data, health indicators, and other related information collected during household interviews as well as the sample design variables. The recommended procedure for variance estimation requires use of stratum and PSU variables (SDMVSTRA and SDMVPSU, respectively) in the demographic data file.

This laboratory data file can be linked to the other NHANES data files using the unique survey participant identifier (i.e., SEQN).

The variable URXUCR (urine creatinine) will not be reported in this file. URXUCR can be found in the data file titled “Albumin & Creatinine – Urine”.

Detection Limits

The detection limits were constant for all of the analytes in the data set. Two variables are provided for each of these analytes. The variable name ending in “LC” (ex., SSPPMALC) indicates whether the result was below the limit of detection: the value “0” means that the result was at or above the limit of detection, “1” indicates that the result was below the limit of detection. The other variable (ex., SSPPMA) provides the analytic result for that analyte. For analytes with analytic results below the lower limit of detection (ex., SSPPMALC=1), an imputed fill value was placed in the analyte results field. This value is the lower limit of detection divided by the square root of 2 (LLOD/sqrt[2]) and rounded to the precision of the LLOD.

The lower limit of detection (LLOD, in ng/mL) for SSPPMA and SSMMAC:

Variable Name	Analyte Name	LLOD
SSPPMA	N-Acetyl-S-(6-hydroxy-2,4-cyclohexadien-1-yl)-L-cysteine (ng/mL)	1.91
SSMMAC	N-Acetyl-S-methyl-L-cysteine (ng/mL)	5.11

References

• Alwis K.U., Blount B.C., Britt A.S., Patel D., Ashley D.L. Simultaneous analysis of 28 urinary VOC metabolites using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS). Anal. Chim. Acta. (2012) 750: 152-160.
• Caudill S.P., Schleicher R.L, Pirkle J.L. Multi-rule quality control for the age-related eye disease study. Stat. Med. (2008) 27(20): 4094-4106.
• IARC. International Agency for Research on Cancer (IARC), Monographs on the Evaluation of carcinogenic risks to humans: overall evaluation of carcinogenicity, Supplement 7. (1987) IARC Publications: Lyon, France. p. 120.
• Konstantinou E., Fotopoulou F., Drosos A., Dimakopoulou N. Tobacco-specific nitrosamines: A literature review. Food. Chem. Toxicol. (2018) 118: 198–203.
• Westgard J.O., Barry P.L., Hunt M.R., Groth T. A multi-rule Shewhart chart for quality control in clinical chemistry. Clin. Chem. (1981) 27: 493-501.

Codebook and Frequencies